REM Sleep Behavior Disorder

Etiology

RBD occurs because of the failure to inhibit spinal motor neurons during REM sleep. A strong association between RBD and the future development of a neurodegenerative disorder has been well established.[2] Neurodegenerative disorders linked to alpha-synuclein positive intracellular inclusions, for example, parkinsonism, Lewy body dementia, and multiple system atrophy (MSA) are associated with alpha-synucleinopathies. Nuclei in the pons control REM sleep. Lesions in pons can lead to the development of these synucleinopathies and RBD.[3] A progressive degeneration of these nuclei may explain the RBD as a prodrome before the full onset of the disease spectrum. Neuroimaging studies have shown progressive dopaminergic abnormalities in patients with RBD.[4] Dopaminergic agents like antidepressants may, therefore, worsen RBD. In narcolepsy, about 50% of patients may manifest RBD. Lack of orexin in narcolepsy may fail to stabilize REM sleep and results in a lack of muscle atonia during REM sleep.[5]

Epidemiology

The overall prevalence of “spontaneous” RBD is estimated to be about 1% in the general population and 2% in older individuals.[6] It is more prevalent in elderly males than females with a male to female ratio of 9 to 1.[7] There is a strong association of RBD with many neurodegenerative disorders. RBD can be a precursor to more serious conditions involving alpha-synuclein neuropathies such as parkinsonism, multiple system atrophy, or dementia with Lewy body where prevalence can be as high as 76% to 81% of affected individuals.[3] In a case series,[8] about half of the patients with RBD converted to a neurologic disorder within 12 years.

Causes of “secondary” RBD, especially in younger individuals, include parkinsonism, narcolepsy, or the use of antidepressant medications. The prevalence of RBD in narcolepsy has been reported to be as high as 36%.[5] Antidepressant medications can precipitate RBD-type symptoms in up to 6% of cases [9]. Other secondary causes of RBD may include vascular lesions, tumors, demyelinating disease, autoimmune, or inflammatory disorders.

Obstructive sleep apnea (OSA) may mimic RBD and is referred to as “pseudo RBD.”[10]

Pathophysiology

There are 2 systems involved in normal REM sleep; one generates muscle atonia and the other suppresses motor-skeletal activity. Muscle atonia involves active inhibition by neurons in the medulla. Locomotion involves input from the forebrain, and the thalamus influences spinal motor neurons. Several brainstem pontine regions have been implicated in RBD pathophysiology including the peri-locus coeruleus region, pedunculo-pontine nucleus (PPN), and laterodorsal tegmental nucleus (LDTN).[11] Supra-spinal mechanism handles REM atonia. During REM sleep, nuclei from the pons excite neurons in the medulla, which then transmit descending inhibitory projections to spinal alpha motor-neurons resulting in hyperpolarization and muscle atonia. It is the disinhibition of these neurons that leads to muscle activity during the REM stage of sleep.[2]

History and Physical

Physicians should get a thorough sleep history regarding nocturnal movements to assess the nature of parasomnia. Sleep history may help to identify whether the symptoms are happening during the REM or non-REM stage of sleep. History of epileptic activity may be explored. Patients themselves may not know of motor activity during sleep. In a study of 203 patients with RBD,[12] only about half of the patients knew of their symptoms. The movements may be short and range in severity. These may include punching, kicking, falling out of bed, gesturing, or knocking over the nightstand. Patients may have vocalizations during an attack. Schenck et al.[13] reported dream enactment in 87% of their study population. Patients had vivid, intense, action-filled, and, violent dreams coincident with the onset of RBD. Sleep-related injuries occurred in 79% of patients in this series of patients.

Symptoms predominantly occur in the second half of the night when the REM sleep is most prevalent and usually occurs during the last REM sleep period.

In milder forms, patients may sleep through the event, but in severe cases, patients may transiently wake up but then fall asleep.

Patients may be examined for the development of any neurodegenerative disorders.

Evaluation

According to the third edition of the International Classification of Sleep Disorders (ICSD-3), a diagnosis of RBD requires all of the following[14]:

• Repeated episodes of sleep-related vocalization and/or complex motor behaviors
• Behaviors are documented by polysomnography to occur during REM sleep or, based on the clinical history of dream enactment, are presumed to occur during REM sleep
• Presence of REM sleep without atonia (RSWA) on polysomnography
• An absence of epileptiform activity during REM sleep, unless RBD can be clearly distinguished from any concurrent REM sleep-related seizure disorder
• Sleep disturbance not better explained by another sleep disorder, medical or neurologic disorder, mental disorder, medication use, or substance use disorder

RBD is the only parasomnia which requires an in-facility polysomnogram to diagnose RBD.

The characteristic polysomnographic finding of RBD is REM sleep without atonia (RSWA). It is an elevation of motor tone during REM sleep as measured by electromyography (EMG) activity in the chin and/or limb leads.[15]

Formal polysomnographic criteria for RSWA developed by the American Academy of Sleep Medicine require either of the following[14]:

• Sustained elevation of chin EMG activity during REM sleep (greater than 50% of the 30-second epoch duration compared with minimum amplitude in non-REM sleep)
• Excessive bursts of transient muscle activity in the chin or limb EMG during REM sleep, defined by the presence of 5 (50%) or more mini-epochs (30-second epoch is divided into 10 sequential 3-second mini-epochs), containing bursts of transient muscle activity. In RBD, excessive transient muscle activity bursts last 0.1 to 5.0 seconds and are at least 4 times as high in amplitude as the background EMD activity.

Optimally, both upper and lower extremity EMG should be used when evaluating for RBD. Alternate EMG derivations that make use of upper extremity EMG to improve sensitivity for detecting RSWA are reviewed separately.

The disorder needs to be differentiated from other parasomnias including both REM and non-REM sleep parasomnias including nightmares, night terrors, sleepwalking, and sleep talking. Periodic leg movements may present with limb movement while sleeping but generally occur during the non-REM stage of the sleep and have distinctive diagnostic criteria on polysomnography.

Epileptic disorders like sleep-related hyperosmolar epilepsy (frontal lobe epilepsy) may present with motor activity during sleep. However, compared with RBD, these patients are generally younger and unaware of their symptoms.

Treatment / Management

The primary goal of treatment is to provide patients with a safe sleeping environment for them and their bed partners. Healthcare professionals can achieve this through non-pharmacologic approaches and pharmacotherapy if needed.

It is important to counsel patients and their bed partners on avoidance of potentially hazardous and injuries objects near the patients, for example, firearms or glass objects. Bed partners should be educated on the disease, and the patient’s enactments during dreams are not under voluntary control.

Sleeping alone may be advisable in severe cases. Many patients may require padded bed rails or must sleep in a sleeping bag.[16]

Patients may be advised to stop SSRI and tricyclic antidepressants that are known to cause or exacerbate RBD.[17](B2)

Regarding pharmacotherapy, melatonin is now considered first-line therapy in the treatment of RBD.[18] Its mechanism of action is unknown, but in doses between 6 to 18 mg, it augments REM atonia and improves RBD symptoms. Patients are typically started at doses of 3 mg, and then doses are increased in 3-mg increments until the RBD symptoms resolve.

Low-dose clonazepam (0.5 to 1 mg at bedtime) has been traditionally used to control RBD symptoms. Its mechanism of action is not clear either but may help suppress unpleasant dreams.[17] Its use may be limited due to side effects. In one study, 39% of patients reported side effects.[12](B2)

Differential Diagnosis

The differential diagnosis of sleep enactment behaviors can include RBD, obstructive sleep apnea, seizures, nocturnal panic attacks, nightmares, and non-REM parasomnias such as night terrors, somnambulism, or confusional arousals. The differences of these disorders can usually be identified with detailed history taking, but a video-monitored polysomnographic study is often warranted.